24-h Ambulatory Systolic Blood Pressure Research Articles

Abstract P161: Randomized Trial Of Magnesium Glycinate Supplementation And Blood Pressure In Middle-aged Adults

Introduction: Magnesium (Mg) intake is inversely associated with BP and hypertension risk in observational studies. However, short-term randomized trials on seated BP have been inconsistent, with few studies measuring 24-h ambulatory BP (ABP). In addition, Mg glycinate, a more easily absorbed form of supplemental Mg, has been largely untested in randomized trials and may serve as a first-line approach for BP reduction among those with elevated, untreated, BP. Methods: We conducted a randomized, double-blind, placebo-controlled trial (NCT03688503) testing 480 mg/d of elemental Mg glycinate versus placebo for 12 weeks among 59 otherwise healthy participants aged 30-74 y with elevated seated BP (systolic BP (SBP) 120-149 mmHg and/or diastolic BP (DBP) 80-94 mmHg) and no history of anti-hypertensive medication use. At baseline, 6 weeks, and 12 weeks, we measured seated BP, monitored 24-h ABP, and collected blood samples. Our primary aim tested Mg glycinate on 12-week changes in seated BP and 24-h ABP, and subgroup analyses considered if sex, age, or baseline BP modified the effect of Mg on BP. Results: Baseline characteristics were equally distributed at randomization (mean age, 57.2 y; 58% men) with mean seated BP of 133.4/82.6 mmHg. Compliance was high (Mg, 87%; placebo, 96%). After 12 weeks, there was no significant effect of Mg glycinate versus placebo on seated SBP (-4.5 vs -1.6 mmHg from baseline; p=0.38) and DBP (-1.9 vs -0.9 mmHg from baseline; p=0.64), nor was there any significant effect on overall, daytime, or nighttime 24-h ambulatory SBP and DBP (all p>0.05). In subgroup analyses, the effect of Mg glycinate on seated SBP was suggestively, but non-significantly, stronger among those with baseline seated SBP ≥130 mmHg (-9.3 vs -2.7 mmHg; p=0.12; p, interaction=0.24) and among women (-9.7 vs -3.1 mmHg; p=0.26; p, interaction=0.29). Age, seated DBP, and mean 24-h ambulatory SBP and DBP did not modify the effects of Mg supplementation. Conclusions: A Mg glycinate supplement did not significantly reduce seated or 24-h BP in adults with elevated, untreated BP. Forthcoming analyses will expand on the role of serum and dietary Mg levels. Larger trials are warranted to elucidate possible effects of Mg glycinate on seated SBP among those with elevated BP and among women.

Effect of aerobic and resistance exercise training on inflammation, endothelial function and ambulatory blood pressure in middle-aged hypertensive patients.

The current randomized controlled trial tested the hypothesis that both aerobic training and dynamic resistance training will improve inflammation, endothelial function and 24-h ambulatory blood pressure (ABP) in middle-aged adults with hypertension, but aerobic training would be more effective. Forty-two hypertensive patients on at least one antihypertensive medication (19 men/23 women; 30-59 years of age) were randomly assigned to 12 weeks of supervised aerobic training (n = 15), resistance training (n = 15) or a nonexercise control (n = 12) group. Inflammation, endothelial function, 24-h ABP and related measures were evaluated at pre and postintervention. We found that aerobic training and resistance training were well tolerated. Both aerobic training and resistance training reduced daytime systolic ABP (-7.2 ± 7.9 and -4.4 ± 5.8 mmHg; P < 0.05) and 24-h systolic ABP (-5.6 ± 6.2 and -3.2 ± 6.4 mmHg; P < 0.05). aerobic training and resistance training both improved brachial artery flow-mediated dilation by 1.7 ± 2.8 and 1.4 ± 2.6%, respectively (7.59 ± 3.36 vs. 9.26 ± 2.93 and 7.24 ± 3.18 vs. 8.58 ± 2.37; pre vs. post P < 0.05). However, only aerobic training decreased markers of inflammation (C-reactive protein, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1 and lectin-like oxidized LDL receptor-1) and endothelin-1 and increased nitrite and nitrate levels (P < 0.05). Healthcare providers should continue to emphasize aerobic training for hypertension management given the established role of nitric oxide, endothelin-1 and chronic low-level inflammation in the pathogenesis of cardiovascular disease. However, our study demonstrates that resistance training should also be encouraged for middle-aged hypertensive patients. Our results also suggest that even if patients are on antihypertensive medications, regular aerobic training and resistance training are beneficial for blood pressure control and cardiovascular disease risk reduction.

Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial

Background: Hypertension often accompanies chronic kidney disease (CKD), and diuretics are widely prescribed to reduce blood pressure (BP). Chlorthalidone (CTD) is a thiazide-like diuretic and an effective antihypertensive drug, yet little data exist to support its use in treating hypertension in individuals with advanced CKD. Methods: Chlorthalidone in Chronic Kidney Disease (CLICK) is a phase II, single-institution, multicenter, double-blind randomized control trial to test the hypothesis that CTD improves BP, through reduction of extracellular fluid volume, and results in target organ protection in patients with stage 4 CKD and poorly controlled hypertension. After a single-blind placebo run-in for 2 weeks and confirmation of hypertension by 24-h ambulatory blood pressure (ABP), patients are randomized to either placebo or CTD 12.5 mg once daily (QD) followed by dose escalation. Randomization is stratified by prior loop diuretic use, and the double-blind phase lasts 12 weeks. With a total of 160 patients, the study will have ≥80% power to detect a 6 mm Hg difference in systolic 24-h ABP between the 2 treatment groups. Results: Between June 2016 and October 2019, 131 patients have been randomized. The baseline characteristics are as follows: average age 65.8 years, 79% men, 36% Black, 79% with diabetes, mean eGFR 23.2 mL/min/1.73 m², median urine albumin/creatinine ratio 923 mg/g, average number of BP medications 3.4, 60% on loop diuretics, and 24-h ABP averaged 141.7/73.8 mm Hg. Conclusion: Among patients with stage 4 CKD and uncontrolled hypertension, CLICK should answer the question whether CTD is safe and effective.

24-h ambulatory blood pressure versus clinic blood pressure as predictors of cardiovascular risk: a systematic review and meta-analysis of prospective studies.

There is uncertainty about the usefulness of ambulatory blood pressure (ABP) in predicting cardiovascular disease (CVD) risk. Our objective was to compare the prognostic value of ABP versus clinic blood pressure (BP) in CVD. We conducted electronic searches on Medline, Embase, and the Cochrane library up to July 2018. We included prospective longitudinal studies that compared 24-h ABP with clinic BP measurement in adults. Our main outcomes were all-cause mortality, CVD mortality, and/or CVD events. We assessed study quality based on four domains and pooled data using a random effects model of STATA for meta-analyses. We included 13 studies comprising 81 736 participants. The overall quality of the studies was moderate. Both systolic and diastolic 24-h ABP as well as systolic clinic BP significantly predicted all-cause mortality, CVD mortality, and CVD events. Systolic 24-h ABP was significantly better than systolic clinic BP at predicting future risk of CVD events: combined hazard ratio for 24-h ABP = 1.27 (95% confidence interval 1.21-1.34) per 10 mmHg increase in SBP compared with 1.13 (1.06-1.21) for clinic BP (interaction test P = 0.02). After adjusting for clinic BP, both systolic and diastolic 24-h ABP measurements were significantly better than their corresponding clinic measurements at predicting all-cause mortality, CVD mortality, and CVD events (P = 0.001 and P = 0.000, respectively). Systolic 24-h ABP is a better predictor of future CVD events than systolic clinic BP. Future studies should incorporate the use of individual patient data to assess the prognostic value of 24-h ABP.

Lipid profile and left ventricular geometry pattern in obese children

BackgroundLeft ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children.Patients and methodsIn this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex.ResultsOur study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12–16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97).ConclusionIncreased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.

Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design

BackgroundThe SPYRAL HTN clinical trial program was initiated with two 80-patient pilot studies, SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED, which provided biological proof of principle that renal denervation has a blood pressure-lowering effect versus sham controls for subjects with uncontrolled hypertension in the absence or presence of antihypertensive medications, respectively.Trial designTwo multicenter, prospective, randomized, sham-controlled trials have been designed to evaluate the safety and efficacy of catheter-based renal denervation for the reduction of blood pressure in subjects with hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) or presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications. The primary efficacy endpoint is baseline-adjusted change from baseline in 24-h ambulatory systolic blood pressure. The primary safety endpoint is incidence of major adverse events at 1 month after randomization (or 6 months in cases of new renal artery stenosis). Both trials utilize a Bayesian design to allow for prespecified interim analyses to take place, and thus, the final sample sizes are dependent on whether enrollment is stopped at the first or second interim analysis. SPYRAL HTN-OFF MED Pivotal will enroll up to 300 subjects and SPYRAL HTN-ON MED Expansion will enroll up to 221 subjects. A novel Bayesian power prior approach will leverage historical information from the pilot studies, with a degree of discounting determined by the level of agreement with data from the prospectively powered studies.ConclusionsThe Bayesian paradigm represents a novel and promising approach in device-based hypertension trials.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02439749 (SPYRAL HTN-OFF MED Pivotal) and NCT02439775 (SPYRAL HTN-ON MED Expansion).

The REDUCE HTN: REINFORCE: Randomized, Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension

ObjectivesThe aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline. BackgroundA blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations. MethodsREDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis. ResultsBaseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis. ConclusionsFuture studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)

Efficacy and Safety of Azilsartan Medoxomil and Telmisartan in Hypertensive Patients: A Randomized, Assessor-Blinded Study.

Background:Few studies have compared the safety and efficacy of azilsartan medoxomil (AZL-M) and telmisartan in hypertensive patients, especially using ambulatory blood pressure monitoring (ABPM).Objective:The objective of this study was to compare the efficacy and safety profile of AZL-M and telmisartan in hypertensive patients using ABPM and clinic blood pressure (BP) monitoring.Materials and Methods:This prospective, randomized, open-label, blinded endpoint, parallel-arm study included 700 patients, aged 18–70 years, with clinic and 24-h mean ambulatory systolic BP (SBP) of 150–180 mmHg and 130–170 mmHg, respectively. They were randomized equally into two groups: Group A received AZL-M 40 mg and Group T received telmisartan 40 mg; the dose was force titrated to 80 mg after 2 weeks if the response rate was not achieved. BP (clinical and ambulatory) was measured after 12 weeks and compared with baseline measurements.Results:AZL-M significantly reduced the 24-h mean ambulatory SBP (Group A: 112.74 ± 7.58 mmHg; Group T: 113.96 ± 8.52 mmHg; P < 0.0001) and diastolic BP (Group A: 71.39 ± 5.89 mmHg; Group T: 67.29 ± 6.79 mmHg; P < 0.0001) compared with telmisartan at week 12. The clinic SBP significantly decreased in Group A at weeks 4 (−30.69± −0.33 mmHg) and 12 (−39.69± −1.09 mmHg) (for both, P = 0.0001). Dose titration was done in 99 and 128 patients from Group A and Group T, respectively (P = 0.012). Headache was the most common adverse drug reaction (Group A: 21; Group T: 27) and fatigue the least.Conclusion:This study found that AZL-M has greater antihypertensive efficacy than telmisartan, with comparable side effects. In addition, ABPM was shown to be a feasible method for such studies.

Susceptibility to diarrhea is related to hemodynamic markers of sympathetic activation in the general population

Objectives: Functional gastrointestinal (GI) symptoms, such as IBS (irritable bowel syndrome), have been suggested to be associated with autonomic neuropathy. We therefore examined associations between hemodynamic indices of autonomic control, functional GI symptoms and stress in a population-based cohort.Methods and materials: The study included 2094 participants of the Malmö Offspring Study (mean age 40.6 ± 13.8 years, 53.9% women). 509 (24.3%) reported having GI symptoms the last 2 weeks, without having organic GI disease, and 347 subjects (16.6%) reported IBS. Office and ambulatory 24-h systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were measured. Associations between hemodynamic parameters and abdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea and psychological well-being according to the visual analog scale for IBS (VAS-IBS), and stress, were performed by Spearman’s correlation test and linear regression models.Results: Subjects who reported GI symptoms had lower office supine and standing DBP and lower 24 h SBP and DBP compared with those without GI symptoms. Regarding specific symptoms, diarrhea was correlated with 24-h measurements of SBP (rs = 0.197), DBP (rs = 0.173) and heart rate (rs = 0.134). Subjects with the most severe diarrhea had higher 24-h SBP (125.2 vs. 119.0 mmHg; p = .038), DBP (74.0 vs. 69.0 mmHg; p = .033) and heart rate (74.5 vs 71.1 beats/minute; p = .048), after adjustments for confounders, compared to the other. There were no associations between other GI symptoms, IBS, stress and hemodynamic alterations.Conclusion: Functional diarrhea was associated with hemodynamic indices of sympathetic activation, supporting a possible role of the autonomic nervous system in diarrhea.

Efficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial

BackgroundClinical data show that due to the limited effects of lifestyle regulation and unsatisfactory drug adherence, only half of the hypertensive population have their blood pressure (BP) under control. In recent years, catheter-based renal denervation (RDN) has been used as a novel approach for treating uncontrolled hypertension. The safety and efficacy of catheter-based RDN have been confirmed by a number of studies and trials in which the participants were all non-Chinese and RDN was conducted via radiofrequency or ultrasound.Methods/designThis study is a prospective multicenter randomized sham-controlled trial that aims to investigate the safety and efficacy of cryoablation RDN (cryo-RDN) using a novel dedicated cryoablation balloon catheter (Cryofocus, China). A total of 200 Chinese patients who have uncontrolled hypertension despite standard medical treatment will be enrolled. With drug standardization, eligible participants will be randomized in a 1:1 ratio to undergo cryo-RDN treatment or renal angiography alone as a sham treatment.The primary endpoint is defined as the change in 24-h ambulatory systolic blood pressure from baseline to 6 months. Office BP and other 24-h ambulatory BP are included as secondary endpoints. Safety endpoints primarily include any adverse effects.DiscussionThis study was designed to verify the safety and efficacy of cryo-RDN with Cryofocus balloon catheters in uncontrolled hypertensive patients on polypharmacy. The aim is to provide a new way to improve the control of hypertension in China as a complement to drug therapy.Trial registrationChiCTR, ChiCTR1800017707. Registered on 10 August 2018.

Effect of coadministration of enriched Korean Red Ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L) on cardiometabolic outcomes in type-2 diabetes: A randomized controlled trial

BackgroundDiabetes mellitus and hypertension often occur together, amplifying cardiovascular disease (CVD) risk and emphasizing the need for a multitargeted treatment approach. American ginseng (AG) and Korean Red Ginseng (KRG) species could improve glycemic control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective was to investigate the therapeutic potential of coadministration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to standard of care therapy, in the management of hypertension and cardiometabolic risk factors in type-2 diabetes. MethodsWithin a randomized controlled, parallel design of 80 participants with type-2 diabetes (HbA1c: 6.5–8%) and hypertension (systolic BP: 140–160 mmHg or treated), supplementation with either 2.25 g/day of combined Rg3-KRG + AG or wheat-bran control was assessed over a 12-wk intervention period. The primary endpoint was ambulatory 24-h systolic BP. Additional endpoints included further hemodynamic assessment, glycemic control, plasma lipids and safety monitoring. ResultsCombined ginseng intervention generated a mean ± SE decrease in primary endpoint of 24-h systolic BP (−3.98 ± 2.0 mmHg, p = 0.04). Additionally, there was a greater reduction in HbA1c (−0.35 ± 0.1% [–3.8 ± 1.1 mmol/mol], p = 0.02), and change in blood lipids: total cholesterol (−0.50 ± 0.2 mmol/l, p = 0.01), non-HDL-C (−0.54 ± 0.2 mmol/l, p = 0.01), triglycerides (−0.40 ± 0.2 mmol/l, p = 0.02) and LDL-C (−0.35 ± 0.2 mmol/l, p = 0.06) at 12 wks, relative to control. No adverse safety outcomes were observed. ConclusionCoadministration of Rg3-KRG + AG is an effective addon for improving BP along with attaining favorable cardiometabolic outcomes in individuals with type 2 diabetes. Ginseng derivatives may offer clinical utility when included in the polypharmacy and lifestyle treatment of diabetes. Clinical trial registrationClinicaltrials.gov identifier, NCT01578837;

EFFECTS OF RENAL DENERVATION IN PATIENTS WITH VERSUS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Activity of the sympathetic nervous system (SNS) is increased in hypertensive patients with chronic kidney disease (CKD). In this updated version, we tested the hypothesis whether hypertensive patients with CKD enrolled in the Global Symplicity Registry (GSR) showed different responses in blood pressure (BP) reduction in the short- and long-term follow-up. Design and method: The GSR (NCT 01534299) is a prospective, open-label, international, multicentre observational study for assessment of safety and effectiveness of renal denervation (RDN) among real-world patients treated with the Symplicity™ RDN system (Medtronic, Santa Rosa, CA, USA). Inclusion criteria are age >= 18 years and eligibility for RDN. Office and 24-h ambulatory BP were assessed at pre-specified time-points (12, 24 and 36 months). For the current updated analyses, enrolled patients (N = 1980) were stratified based on baseline estimated glomerular filtration rate in <60 vs. >= 60 ml/min/1.73m2 into with (N = 475) and without (N = 1505) CKD groups. Results: Patients with CKD were significantly older (p < 0.0001) and more likely to be female (p = 0.0027) compared to patients without CKD. At baseline office systolic BP was lower (162.4 ± 26 vs. 165.8 ± 24 mmHg, p = 0.0113), whereas there was no difference in baseline 24-h ambulatory systolic BP (153.6 ± 19 vs. 153.7 ± 18 mmHg, p = 0.9162), in patients with, compared to without CKD. In patients with and without CKD, office as well as 24-h ambulatory BP were significantly reduced after RDN compared to baseline values at all time-points (all p < 0.001). There was a greater office systolic BP reduction in favor of patients without compared to with CKD, whereas no difference in 24-h ambulatory systolic BP reduction after RDN, even after adjustment (Table), was observed.Conclusions: After adjustment for baseline data, BP reduction after RDN showed a disparate response pattern in office and 24-h ambulatory BP reductions in patients with CKD. Data needs to be confirmed by a rigorously conducted, prospective, double-blind, sham-controlled study.

Guiding Hypertension Management Using Different Blood Pressure Monitoring Strategies (GYMNs study): comparison of three different blood pressure measurement methods: study protocol for a randomized controlled trial

BackgroundHome blood pressure (BP) and unattended automated BP (uAOBP) monitoring have been recommended by guidelines for the care of hypertensive subjects. However, BP measurements in the peripheral arteries cannot serve as direct substitutes for their central counterparts. Moreover, the comparative effectiveness and safety of BP-guided strategies using these BP measuring devices have never been evaluated.Methods/designPatients with uncontrolled or newly diagnosed hypertension aged 20–90 years will be recruited via outpatient clinics and allocated into three arms by stratified randomization (baseline systolic BP 130–155 mmHg and 155–180 mmHg): home BP, uAOBP, and central BP-guided treatment. At each scheduled visit to the clinic, a patient’s BP will be measured by each of the three methods of measuring BP. The blood pressure from three different methods will be confirmed available at each visit. Patients and physicians will be blinded to the allocated interventions because they will use measured BP values in the clinic through a standardized report format. A common BP target for systolic blood pressure (SBP) of 130 mmHg is adopted for these BP-guided strategies. The primary outcome is the change of 24-h mean ambulatory SBP at 3 months. A key secondary outcome is to determine the percentage achieving their target BPs at 3 months and the decrease of left ventricular mass at 12 months.DiscussionTo our knowledge, this is the first prospective double-blind randomized controlled trial to assess the optimal guiding strategy for hypertension. It will help to define which BP monitoring method is the most effective for guiding the clinical management of hypertension. It will provide good evidence to support future guideline recommendations for BP monitoring devices.Trial registrationClinicalTrials.gov, NCT03578848. Registered on 4 June 2018.

Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension.

Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion. From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed. Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27mmHg and 148 ± 16mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29mmHg (p < 0.01), 24-h systolic BP to 142 ± 22mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015). The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.

Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension

BackgroundThere are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension. ObjectivesThe purpose of this study was to evaluate the blood pressure (BP) response after RSD in sham-controlled randomized trials. MethodsDatabases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis. ResultsThe analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than sham procedure (WMD −3.65 mm Hg, 95% CI: −5.33 to −1.98; p < 0.001). Compared with sham, RSD was also associated with a significant decrease in daytime ASBP (WMD −4.07 mm Hg, 95% CI: −6.46 to −1.68; p < 0.001), office systolic BP (WMD −5.53 mm Hg, 95% CI: −8.18 to −2.87; p < 0.001), 24-h ambulatory diastolic BP (WMD −1.71 mm Hg, 95% CI: −3.06 to −0.35; p = 0.01), daytime ambulatory diastolic BP (WMD −1.57 mm Hg, 95% CI: −2.73 to −0.42; p = 0.008), and office diastolic BP (WMD −3.37 mm Hg, 95% CI: −4.86 to −1.88; p < 0.001). Compared with first-generation trials, a significantly greater reduction in daytime ASBP was observed with RSD in second-generation trials (6.12 mm Hg vs. 2.14 mm Hg; p interaction = 0.04); however, this interaction was not significant for 24-h ASBP (4.85 mm Hg vs. 2.23 mm Hg; p interaction = 0.13). ConclusionsRSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial

BackgroundEmpagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness.MethodsOur analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial (http://www.ClinicalTrials.gov: NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis.ResultsAs previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = − 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found.ConclusionBesides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms.Trial registrationhttp://www.ClinicalTrials.gov: NCT02471963, registered 15th June 2015, retrospectively registered

Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry.

AimsSeveral studies and registries have demonstrated sustained reductions in blood pressure (BP) after renal denervation (RDN). The long-term safety and efficacy after RDN in real-world patients with uncontrolled hypertension, however, remains unknown. The objective of this study was to assess the long-term safety and efficacy of RDN, including its effects on renal function.Methods and resultsThe Global SYMPLICITY Registry is a prospective, open-label registry conducted at 196 active sites worldwide in hypertensive patients receiving RDN treatment. Among 2237 patients enrolled and treated with the SYMPLICITY Flex catheter, 1742 were eligible for follow-up at 3 years. Baseline office and 24-h ambulatory systolic BP (SBP) were 166 ± 25 and 154 ± 18 mmHg, respectively. SBP reduction after RDN was sustained over 3 years, including decreases in both office (−16.5 ± 28.6 mmHg, P < 0.001) and 24-h ambulatory SBP (−8.0 ± 20.0 mmHg; P < 0.001). Twenty-one percent of patients had a baseline estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Between baseline and 3 years, renal function declined by 7.1 mL/min/1.73 m2 in patients without chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m2; baseline eGFR 87 ± 17 mL/min/1.73 m2) and by 3.7 mL/min/1.73 m2 in patients with CKD (eGFR <60 mL/min/1.73 m2; baseline eGFR 47 ± 11 mL/min/1.73 m2). No long-term safety concerns were observed following the RDN procedure.ConclusionLong-term data from the Global SYMPLICITY Registry representing the largest available cohort of hypertensive patients receiving RDN in a real-world clinical setting demonstrate both the safety and efficacy of the procedure with significant and sustained office and ambulatory BP reductions out to 3 years.

Physical Activity In Renal Disease (PAIRED) and the effect on hypertension: study protocol for a randomized controlled trial

BackgroundThe prevalence of hypertension among people with chronic kidney disease is high with over 60% of people not attaining recommended targets despite taking multiple medications. Given the health and economic implications of hypertension, additional strategies are needed. Exercise is an effective strategy for reducing blood pressure in the general population; however, it is not known whether exercise would have a comparable benefit in people with moderate to advanced chronic kidney disease and hypertension.MethodsThis is a parallel-arm trial of adults with hypertension (systolic blood pressure greater than 130 mmHg) and an estimated glomerular filtration rate of 15–45 ml/min 1.73 m2. A total of 160 participants will be randomized, with stratification for estimated glomerular filtration rate, to a 24-week, aerobic-based exercise intervention or enhanced usual care. The primary outcome is the difference in 24-h ambulatory systolic blood pressure after 8 weeks of exercise training. Secondary outcomes at 8 and 24 weeks include: other measurements of blood pressure, aortic stiffness (pulse-wave velocity), change in the Defined Daily Dose of anti-hypertensive drugs, medication adherence, markers of cardiovascular risk, physical fitness (cardiopulmonary exercise testing), 7-day accelerometry, quality of life, and adverse events. The effect of exercise on renal function will be evaluated in an exploratory analysis. The intervention is a thrice-weekly, moderate-intensity aerobic exercise supplemented with isometric resistance exercise delivered in two phases. Phase 1: supervised, facility-based, weekly and home-based sessions (8 weeks). Phase 2: home-based sessions (16 weeks).DiscussionTo our knowledge, this study is the first trial designed to provide a precise estimate of the effect of exercise on blood pressure in people with moderate to severe CKD and hypertension. The findings from this study should address a significant knowledge gap in hypertension management in CKD and inform the design of a larger study on the effect of exercise on CKD progression.Trial registrationClinicalTrials.gov, ID: NCT03551119. Registered on 11 June 2018.

Central systolic blood pressure and central pulse pressure predict left ventricular hypertrophy in hypertensive children

BackgroundCentral systolic and pulse pressures are stronger predictors of cardiovascular risk and hypertensive organ damage than brachial blood pressure. It is suggested that isolated systolic hypertension typically seen in adolescents is associated with normal central blood pressure and does not lead to organ damage and this phenomenon is called spurious hypertension.MethodsWe assessed the prevalence of spurious hypertension and analyzed utility of pulse wave analysis as determinant of hypertensive organ damage in 294 children (62 girls; 15.0 ± 2.4 years) diagnosed as primary hypertension. White coat hypertension, ambulatory prehypertension, ambulatory hypertension, and severe ambulatory hypertension were diagnosed in 127, 29, 41, and 97 patients, respectively.ResultsNormal central blood pressure was found in 100% in patients with white coat hypertension, 93% in pre-hypertensives, 51.2% in those with ambulatory hypertension, and 27.8% with severe ambulatory hypertension (p = 0.0001). Children with severe ambulatory hypertension had higher central systolic and pulse pressure, pulse wave velocity, and greater prevalence of left ventricular hypertrophy than white coat and prehypertensive children (p < 0.05). Left ventricular mass index and carotid intima-media thickness correlated with central systolic and pulse pressure (p < 0.05 for all). Receiver operating curve area was similar for augmentation pressure (0.5836), 24-h ambulatory systolic blood pressure (0.5841), central systolic blood pressure (0.6090), and central pulse pressure (0.5611) as predictors of left ventricular hypertrophy.ConclusionsThese findings suggest that pulse wave analysis is complementary to ambulatory blood pressure monitoring in assessment of risk of organ damage in hypertensive adolescents.

Comparing Office, Central, Home and Ambulatory Blood Pressure in Predicting Left Ventricular Mass

The blood pressure measurement method that more accurately predicts a left ventricular mass is controversial, and the evidence suggesting superiority of central over brachial measurements is contradictory. The aim of this study was to compare the relationship between the different clinic and out-of-clinic blood pressure measurements methods with left ventricular mass in patients who attended a specialised hypertension centre for a central blood pressure measurement. An analysis was performed on the correlations between left ventricular mass and central and brachial blood pressure measurements made in the clinic, and home, as well as 24-h systolic blood pressure measurements. A linear regression analysis was then performed to assess the independent relationship of each blood pressure measurement with left ventricular mass. The results on 824 treated and 123 untreated patients showed no significant differences between correlations, although home readings tended to have the best correlations. In regression adjusted models, for each 10 mmHg increase in systolic home blood pressure the left ventricular mass increased 10 g/m2 (95% CI; 3.7-27, p=.01, adjR2 0.38), and for 24-h ambulatory systolic blood pressure it increased 2.3 g/m2 (95% CI 0.76-3.9, p<.01, adjR2 0.15) in treated and untreated patients, respectively. The association of systolic blood pressure with left ventricular mass was better explained by home and 24-h ambulatory monitoring than to clinic-based measurements in treated and untreated patients, respectively. In the clinic, however, the central measurement was not superior to brachial blood pressure.